Leptin resistance elicits depressive-like behaviors in rats

V. A. Macht, M. Vazquez, C. E. Petyak, C. A. Grillo, K. Kaigler, R. T. Enos, J. L. McClellan, T. L. Cranford, E. A. Murphy, J. F. Nyland, G. Solomon, A. Gertler, M. A. Wilson, L. P. Reagan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

There is a growing appreciation that the complications of obesity extend to the central nervous system (CNS) and include increased risk for development of neuropsychiatric co-morbidities such as depressive illness. The neurological consequences of obesity may develop as a continuum and involve a progression of pathological features which is initiated by leptin resistance. Leptin resistance is a hallmark feature of obesity, but it is unknown whether leptin resistance or blockage of leptin action is casually linked to the neurological changes which underlie depressive-like phenotypes. Accordingly, the aim of the current study was to examine whether chronic administration of a pegylated leptin receptor antagonist (Peg-LRA) elicits depressive-like behaviors in adult male rats. Peg-LRA administration resulted in endocrine and metabolic features that are characteristic of an obesity phenotype. Peg-LRA rats also exhibited increased immobility in the forced swim test, depressive-like behaviors that were accompanied by indices of peripheral inflammation. These results demonstrate that leptin resistance elicits an obesity phenotype that is characterized by peripheral immune changes and depressive-like behaviors in rats, supporting the concept that co-morbid obesity and depressive illness develop as a continuum resulting from changes in the peripheral endocrine and metabolic milieu.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalBrain, Behavior, and Immunity
Volume60
DOIs
StatePublished - 1 Feb 2017

Bibliographical note

Publisher Copyright:
© 2016

Keywords

  • Activated T cells
  • Adiposity
  • C-reactive protein
  • Forced swim test
  • Inflammation
  • Obesity
  • Pegylated leptin receptor antagonist
  • Spleen
  • Triglycerides

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